There is considerable hemodynamic evidence suggesting that an increase in vascular smooth muscle mass plays an important role in elevation of peripheral resistance in chronic hypertension. However, quantitative morphometric data describing alterations in smooth muscle mass in resistance vessels are not complete, and there are no quantitative data describing whether these changes in mass are due to cellular hypertrophy or cellular hyperplasia. This proposal has three overall objectives. (1) The first objective is to morphometrically assess differences in smooth muscle mass between small arteries and arterioles (40-300Mum diameter) of spontaneously hypertensive and normotensive Wistar Kyoto rats, and to determine the relative contributions of smooth muscle cell hypertrophy and hyperplasia to these differences. (2) The second objective is to characterize the roles of elevated blood pressure and altered adrenergic nerve function in inducing the smooth muscle cell growth response in hypertension. (3) The third objective relates to my previous observations that there were at least two distinct types of vascular smooth muscle cells in rat aortas, i.e., diploid cells and tetraploid cells; that large increases in the frequency of tetraploid smooth muscle cells were found in aortas of hypertensive rats; and that tetraploid cells had from 70 to 140 percent greater protein mass than diploid cells. My third objective is to utilize a fluorescent activated cell sorter to separate diploid and tetraploid cells on the basis of DNA content, and to then determine whether tetraploid hypertrophic smooth muscle cells have altered structural, functional or biochemical properties. I will examine their growth state, contractile protein content, morphology, angiotensin II binding characteristics, and electrophysiological properties. Beyond their significance for hypertension, the proposed studies have very important implications regarding our understanding of both the physiological and pathological growth of vascular smooth muscle, and will provide definitive data describing changes that occur in hypertrophic smooth muscle cells. Studies will utilize flow microfluorimetry, cell sorting, quantitative microspectrophotometry, autoradiography and morphometry, as well as light and electron microscopy.